@article{12707, abstract = {We establish precise right-tail small deviation estimates for the largest eigenvalue of real symmetric and complex Hermitian matrices whose entries are independent random variables with uniformly bounded moments. The proof relies on a Green function comparison along a continuous interpolating matrix flow for a long time. Less precise estimates are also obtained in the left tail.}, author = {Erdös, László and Xu, Yuanyuan}, issn = {1350-7265}, journal = {Bernoulli}, number = {2}, pages = {1063--1079}, publisher = {Bernoulli Society for Mathematical Statistics and Probability}, title = {{Small deviation estimates for the largest eigenvalue of Wigner matrices}}, doi = {10.3150/22-BEJ1490}, volume = {29}, year = {2023}, } @article{12708, abstract = {Self-organisation is the spontaneous emergence of spatio-temporal structures and patterns from the interaction of smaller individual units. Examples are found across many scales in very different systems and scientific disciplines, from physics, materials science and robotics to biology, geophysics and astronomy. Recent research has highlighted how self-organisation can be both mediated and controlled by confinement. Confinement is an action over a system that limits its units’ translational and rotational degrees of freedom, thus also influencing the system's phase space probability density; it can function as either a catalyst or inhibitor of self-organisation. Confinement can then become a means to actively steer the emergence or suppression of collective phenomena in space and time. Here, to provide a common framework and perspective for future research, we examine the role of confinement in the self-organisation of soft-matter systems and identify overarching scientific challenges that need to be addressed to harness its full scientific and technological potential in soft matter and related fields. By drawing analogies with other disciplines, this framework will accelerate a common deeper understanding of self-organisation and trigger the development of innovative strategies to steer it using confinement, with impact on, e.g., the design of smarter materials, tissue engineering for biomedicine and in guiding active matter.}, author = {Araújo, Nuno A.M. and Janssen, Liesbeth M.C. and Barois, Thomas and Boffetta, Guido and Cohen, Itai and Corbetta, Alessandro and Dauchot, Olivier and Dijkstra, Marjolein and Durham, William M. and Dussutour, Audrey and Garnier, Simon and Gelderblom, Hanneke and Golestanian, Ramin and Isa, Lucio and Koenderink, Gijsje H. and Löwen, Hartmut and Metzler, Ralf and Polin, Marco and Royall, C. Patrick and Šarić, Anđela and Sengupta, Anupam and Sykes, Cécile and Trianni, Vito and Tuval, Idan and Vogel, Nicolas and Yeomans, Julia M. and Zuriguel, Iker and Marin, Alvaro and Volpe, Giorgio}, issn = {1744-6848}, journal = {Soft Matter}, pages = {1695--1704}, publisher = {Royal Society of Chemistry}, title = {{Steering self-organisation through confinement}}, doi = {10.1039/d2sm01562e}, volume = {19}, year = {2023}, } @article{12709, abstract = {Given a finite set A ⊂ ℝ^d, let Cov_{r,k} denote the set of all points within distance r to at least k points of A. Allowing r and k to vary, we obtain a 2-parameter family of spaces that grow larger when r increases or k decreases, called the multicover bifiltration. Motivated by the problem of computing the homology of this bifiltration, we introduce two closely related combinatorial bifiltrations, one polyhedral and the other simplicial, which are both topologically equivalent to the multicover bifiltration and far smaller than a Čech-based model considered in prior work of Sheehy. Our polyhedral construction is a bifiltration of the rhomboid tiling of Edelsbrunner and Osang, and can be efficiently computed using a variant of an algorithm given by these authors as well. Using an implementation for dimension 2 and 3, we provide experimental results. Our simplicial construction is useful for understanding the polyhedral construction and proving its correctness.}, author = {Corbet, René and Kerber, Michael and Lesnick, Michael and Osang, Georg F}, issn = {1432-0444}, journal = {Discrete and Computational Geometry}, pages = {376--405}, publisher = {Springer Nature}, title = {{Computing the multicover bifiltration}}, doi = {10.1007/s00454-022-00476-8}, volume = {70}, year = {2023}, } @article{12710, abstract = {Surface curvature both emerges from, and influences the behavior of, living objects at length scales ranging from cell membranes to single cells to tissues and organs. The relevance of surface curvature in biology is supported by numerous experimental and theoretical investigations in recent years. In this review, first, a brief introduction to the key ideas of surface curvature in the context of biological systems is given and the challenges that arise when measuring surface curvature are discussed. Giving an overview of the emergence of curvature in biological systems, its significance at different length scales becomes apparent. On the other hand, summarizing current findings also shows that both single cells and entire cell sheets, tissues or organisms respond to curvature by modulating their shape and their migration behavior. Finally, the interplay between the distribution of morphogens or micro-organisms and the emergence of curvature across length scales is addressed with examples demonstrating these key mechanistic principles of morphogenesis. Overall, this review highlights that curved interfaces are not merely a passive by-product of the chemical, biological, and mechanical processes but that curvature acts also as a signal that co-determines these processes.}, author = {Schamberger, Barbara and Ziege, Ricardo and Anselme, Karine and Ben Amar, Martine and Bykowski, Michał and Castro, André P.G. and Cipitria, Amaia and Coles, Rhoslyn A. and Dimova, Rumiana and Eder, Michaela and Ehrig, Sebastian and Escudero, Luis M. and Evans, Myfanwy E. and Fernandes, Paulo R. and Fratzl, Peter and Geris, Liesbet and Gierlinger, Notburga and Hannezo, Edouard B and Iglič, Aleš and Kirkensgaard, Jacob J.K. and Kollmannsberger, Philip and Kowalewska, Łucja and Kurniawan, Nicholas A. and Papantoniou, Ioannis and Pieuchot, Laurent and Pires, Tiago H.V. and Renner, Lars D. and Sageman-Furnas, Andrew O. and Schröder-Turk, Gerd E. and Sengupta, Anupam and Sharma, Vikas R. and Tagua, Antonio and Tomba, Caterina and Trepat, Xavier and Waters, Sarah L. and Yeo, Edwina F. and Roschger, Andreas and Bidan, Cécile M. and Dunlop, John W.C.}, issn = {1521-4095}, journal = {Advanced Materials}, number = {13}, publisher = {Wiley}, title = {{Curvature in biological systems: Its quantification, emergence, and implications across the scales}}, doi = {10.1002/adma.202206110}, volume = {35}, year = {2023}, } @article{12719, abstract = {Background Epigenetic clocks can track both chronological age (cAge) and biological age (bAge). The latter is typically defined by physiological biomarkers and risk of adverse health outcomes, including all-cause mortality. As cohort sample sizes increase, estimates of cAge and bAge become more precise. Here, we aim to develop accurate epigenetic predictors of cAge and bAge, whilst improving our understanding of their epigenomic architecture. Methods First, we perform large-scale (N = 18,413) epigenome-wide association studies (EWAS) of chronological age and all-cause mortality. Next, to create a cAge predictor, we use methylation data from 24,674 participants from the Generation Scotland study, the Lothian Birth Cohorts (LBC) of 1921 and 1936, and 8 other cohorts with publicly available data. In addition, we train a predictor of time to all-cause mortality as a proxy for bAge using the Generation Scotland cohort (1214 observed deaths). For this purpose, we use epigenetic surrogates (EpiScores) for 109 plasma proteins and the 8 component parts of GrimAge, one of the current best epigenetic predictors of survival. We test this bAge predictor in four external cohorts (LBC1921, LBC1936, the Framingham Heart Study and the Women’s Health Initiative study). Results Through the inclusion of linear and non-linear age-CpG associations from the EWAS, feature pre-selection in advance of elastic net regression, and a leave-one-cohort-out (LOCO) cross-validation framework, we obtain cAge prediction with a median absolute error equal to 2.3 years. Our bAge predictor was found to slightly outperform GrimAge in terms of the strength of its association to survival (HRGrimAge = 1.47 [1.40, 1.54] with p = 1.08 × 10−52, and HRbAge = 1.52 [1.44, 1.59] with p = 2.20 × 10−60). Finally, we introduce MethylBrowsR, an online tool to visualise epigenome-wide CpG-age associations. Conclusions The integration of multiple large datasets, EpiScores, non-linear DNAm effects, and new approaches to feature selection has facilitated improvements to the blood-based epigenetic prediction of biological and chronological age.}, author = {Bernabeu, Elena and Mccartney, Daniel L. and Gadd, Danni A. and Hillary, Robert F. and Lu, Ake T. and Murphy, Lee and Wrobel, Nicola and Campbell, Archie and Harris, Sarah E. and Liewald, David and Hayward, Caroline and Sudlow, Cathie and Cox, Simon R. and Evans, Kathryn L. and Horvath, Steve and Mcintosh, Andrew M. and Robinson, Matthew Richard and Vallejos, Catalina A. and Marioni, Riccardo E.}, issn = {1756-994X}, journal = {Genome Medicine}, publisher = {Springer Nature}, title = {{Refining epigenetic prediction of chronological and biological age}}, doi = {10.1186/s13073-023-01161-y}, volume = {15}, year = {2023}, } @inbook{12720, abstract = {Here we describe the in vivo DNA assembly approach, where molecular cloning procedures are performed using an E. coli recA-independent recombination pathway, which assembles linear fragments of DNA with short homologous termini. This pathway is present in all standard laboratory E. coli strains and, by bypassing the need for in vitro DNA assembly, allows simplified molecular cloning to be performed without the plasmid instability issues associated with specialized recombination-cloning bacterial strains. The methodology requires specific primer design and can perform all standard plasmid modifications (insertions, deletions, mutagenesis, and sub-cloning) in a rapid, simple, and cost-efficient manner, as it does not require commercial kits or specialized bacterial strains. Additionally, this approach can be used to perform complex procedures such as multiple modifications to a plasmid, as up to 6 linear fragments can be assembled in vivo by this recombination pathway. Procedures generally require less than 3 h, involving PCR amplification, DpnI digestion of template DNA, and transformation, upon which circular plasmids are assembled. In this chapter we describe the requirements, procedure, and potential pitfalls when using this technique, as well as protocol variations to overcome the most common issues.}, author = {Arroyo-Urea, Sandra and Watson, Jake and García-Nafría, Javier}, booktitle = {DNA Manipulation and Analysis}, editor = {Scarlett, Garry}, isbn = {978-1-0716-3003-7}, issn = {1940-6029}, pages = {33--44}, publisher = {Springer Nature}, title = {{Molecular Cloning Using In Vivo DNA Assembly}}, doi = {10.1007/978-1-0716-3004-4_3}, volume = {2633}, year = {2023}, } @article{12723, abstract = {Lead halide perovskites enjoy a number of remarkable optoelectronic properties. To explain their origin, it is necessary to study how electromagnetic fields interact with these systems. We address this problem here by studying two classical quantities: Faraday rotation and the complex refractive index in a paradigmatic perovskite CH3NH3PbBr3 in a broad wavelength range. We find that the minimal coupling of electromagnetic fields to the k⋅p Hamiltonian is insufficient to describe the observed data even on the qualitative level. To amend this, we demonstrate that there exists a relevant atomic-level coupling between electromagnetic fields and the spin degree of freedom. This spin-electric coupling allows for quantitative description of a number of previous as well as present experimental data. In particular, we use it here to show that the Faraday effect in lead halide perovskites is dominated by the Zeeman splitting of the energy levels and has a substantial beyond-Becquerel contribution. Finally, we present general symmetry-based phenomenological arguments that in the low-energy limit our effective model includes all basis coupling terms to the electromagnetic field in the linear order.}, author = {Volosniev, Artem and Shiva Kumar, Abhishek and Lorenc, Dusan and Ashourishokri, Younes and Zhumekenov, Ayan A. and Bakr, Osman M. and Lemeshko, Mikhail and Alpichshev, Zhanybek}, issn = {1079-7114}, journal = {Physical Review Letters}, keywords = {General Physics and Astronomy}, number = {10}, publisher = {American Physical Society}, title = {{Spin-electric coupling in lead halide perovskites}}, doi = {10.1103/physrevlett.130.106901}, volume = {130}, year = {2023}, } @article{12724, abstract = {We use general symmetry-based arguments to construct an effective model suitable for studying optical properties of lead halide perovskites. To build the model, we identify an atomic-level interaction between electromagnetic fields and the spin degree of freedom that should be added to a minimally coupled k⋅p Hamiltonian. As a first application, we study two basic optical characteristics of the material: the Verdet constant and the refractive index. Beyond these linear characteristics of the material, the model is suitable for calculating nonlinear effects such as the third-order optical susceptibility. Analysis of this quantity shows that the geometrical properties of the spin-electric term imply isotropic optical response of the system, and that optical anisotropy of lead halide perovskites is a manifestation of hopping of charge carriers. To illustrate this, we discuss third-harmonic generation.}, author = {Volosniev, Artem and Shiva Kumar, Abhishek and Lorenc, Dusan and Ashourishokri, Younes and Zhumekenov, Ayan and Bakr, Osman M. and Lemeshko, Mikhail and Alpichshev, Zhanybek}, issn = {2469-9969}, journal = {Physical Review B}, number = {12}, publisher = {American Physical Society}, title = {{Effective model for studying optical properties of lead halide perovskites}}, doi = {10.1103/physrevb.107.125201}, volume = {107}, year = {2023}, } @inproceedings{12735, abstract = {Asynchronous programming has gained significant popularity over the last decade: support for this programming pattern is available in many popular languages via libraries and native language implementations, typically in the form of coroutines or the async/await construct. Instead of programming via shared memory, this concept assumes implicit synchronization through message passing. The key data structure enabling such communication is the rendezvous channel. Roughly, a rendezvous channel is a blocking queue of size zero, so both send(e) and receive() operations wait for each other, performing a rendezvous when they meet. To optimize the message passing pattern, channels are usually equipped with a fixed-size buffer, so sends do not suspend and put elements into the buffer until its capacity is exceeded. This primitive is known as a buffered channel. This paper presents a fast and scalable algorithm for both rendezvous and buffered channels. Similarly to modern queues, our solution is based on an infinite array with two positional counters for send(e) and receive() operations, leveraging the unconditional Fetch-And-Add instruction to update them. Yet, the algorithm requires non-trivial modifications of this classic pattern, in order to support the full channel semantics, such as buffering and cancellation of waiting requests. We compare the performance of our solution to that of the Kotlin implementation, as well as against other academic proposals, showing up to 9.8× speedup. To showcase its expressiveness and performance, we also integrated the proposed algorithm into the standard Kotlin Coroutines library, replacing the previous channel implementations.}, author = {Koval, Nikita and Alistarh, Dan-Adrian and Elizarov, Roman}, booktitle = {Proceedings of the ACM SIGPLAN Symposium on Principles and Practice of Parallel Programming}, isbn = {9798400700156}, location = {Montreal, QC, Canada}, pages = {107--118}, publisher = {Association for Computing Machinery}, title = {{Fast and scalable channels in Kotlin Coroutines}}, doi = {10.1145/3572848.3577481}, year = {2023}, } @misc{12736, abstract = {Although a wide variety of handcrafted concurrent data structures have been proposed, there is considerable interest in universal approaches (Universal Constructions or UCs) for building concurrent data structures. UCs (semi-)automatically convert a sequential data structure into a concurrent one. The simplest approach uses locks [3, 6] that protect a sequential data structure and allow only one process to access it at a time. However, the resulting data structure is blocking. Most work on UCs instead focuses on obtaining non-blocking progress guarantees such as obstruction-freedom, lock-freedom or wait-freedom. Many non-blocking UCs have appeared. Key examples include the seminal wait-free UC [2] by Herlihy, a NUMA-aware UC [10] by Yi et al., and an efficient UC for large objects [1] by Fatourou et al.}, author = {Aksenov, Vitaly and Brown, Trevor A and Fedorov, Alexander and Kokorin, Ilya}, booktitle = {Proceedings of the ACM SIGPLAN Symposium on Principles and Practice of Parallel Programming}, isbn = {9798400700156}, location = {Montreal, QB, Canada}, pages = {438--440}, publisher = {Association for Computing Machinery}, title = {{Unexpected scaling in path copying trees}}, doi = {10.1145/3572848.3577512}, year = {2023}, } @article{12737, abstract = {The substitution of heavier, more metallic atoms into classical organic ligand frameworks provides an important strategy for tuning ligand properties, such as ligand bite and donor character, and is the basis for the emerging area of main-group supramolecular chemistry. In this paper, we explore two new ligands [E(2-Me-8-qy)3] [E = Sb (1), Bi (2); qy = quinolyl], allowing a fundamental comparison of their coordination behavior with classical tris(2-pyridyl) ligands of the type [E′(2-py)3] (E = a range of bridgehead atoms and groups, py = pyridyl). A range of new coordination modes to Cu+, Ag+, and Au+ is seen for 1 and 2, in the absence of steric constraints at the bridgehead and with their more remote N-donor atoms. A particular feature is the adaptive nature of these new ligands, with the ability to adjust coordination mode in response to the hard–soft character of coordinated metal ions, influenced also by the character of the bridgehead atom (Sb or Bi). These features can be seen in a comparison between [Cu2{Sb(2-Me-8-qy)3}2](PF6)2 (1·CuPF6) and [Cu{Bi(2-Me-8-qy)3}](PF6) (2·CuPF6), the first containing a dimeric cation in which 1 adopts an unprecedented intramolecular N,N,Sb-coordination mode while in the second, 2 adopts an unusual N,N,(π-)C coordination mode. In contrast, the previously reported analogous ligands [E(6-Me-2-py)3] (E = Sb, Bi; 2-py = 2-pyridyl) show a tris-chelating mode in their complexes with CuPF6, which is typical for the extensive tris(2-pyridyl) family with a range of metals. The greater polarity of the Bi–C bond in 2 results in ligand transfer reactions with Au(I). Although this reactivity is not in itself unusual, the characterization of several products by single-crystal X-ray diffraction provides snapshots of the ligand transfer reaction involved, with one of the products (the bimetallic complex [(BiCl){ClAu2(2-Me-8-qy)3}] (8)) containing a Au2Bi core in which the shortest Au → Bi donor–acceptor bond to date is observed.}, author = {García-Romero, Álvaro and Waters, Jessica E. and Jethwa, Rajesh B and Bond, Andrew D. and Colebatch, Annie L. and García-Rodríguez, Raúl and Wright, Dominic S.}, issn = {1520-510X}, journal = {Inorganic Chemistry}, number = {11}, pages = {4625--4636}, publisher = {American Chemical Society}, title = {{Highly adaptive nature of group 15 tris(quinolyl) ligands─studies with coinage metals}}, doi = {10.1021/acs.inorgchem.3c00057}, volume = {62}, year = {2023}, } @article{12747, abstract = {Muscle degeneration is the most prevalent cause for frailty and dependency in inherited diseases and ageing. Elucidation of pathophysiological mechanisms, as well as effective treatments for muscle diseases, represents an important goal in improving human health. Here, we show that the lipid synthesis enzyme phosphatidylethanolamine cytidyltransferase (PCYT2/ECT) is critical to muscle health. Human deficiency in PCYT2 causes a severe disease with failure to thrive and progressive weakness. pcyt2-mutant zebrafish and muscle-specific Pcyt2-knockout mice recapitulate the participant phenotypes, with failure to thrive, progressive muscle weakness and accelerated ageing. Mechanistically, muscle Pcyt2 deficiency affects cellular bioenergetics and membrane lipid bilayer structure and stability. PCYT2 activity declines in ageing muscles of mice and humans, and adeno-associated virus-based delivery of PCYT2 ameliorates muscle weakness in Pcyt2-knockout and old mice, offering a therapy for individuals with a rare disease and muscle ageing. Thus, PCYT2 plays a fundamental and conserved role in vertebrate muscle health, linking PCYT2 and PCYT2-synthesized lipids to severe muscle dystrophy and ageing.}, author = {Cikes, Domagoj and Elsayad, Kareem and Sezgin, Erdinc and Koitai, Erika and Ferenc, Torma and Orthofer, Michael and Yarwood, Rebecca and Heinz, Leonhard X. and Sedlyarov, Vitaly and Darwish-Miranda, Nasser and Taylor, Adrian and Grapentine, Sophie and al-Murshedi, Fathiya and Abot, Anne and Weidinger, Adelheid and Kutchukian, Candice and Sanchez, Colline and Cronin, Shane J. F. and Novatchkova, Maria and Kavirayani, Anoop and Schuetz, Thomas and Haubner, Bernhard and Haas, Lisa and Hagelkruys, Astrid and Jackowski, Suzanne and Kozlov, Andrey and Jacquemond, Vincent and Knauf, Claude and Superti-Furga, Giulio and Rullman, Eric and Gustafsson, Thomas and McDermot, John and Lowe, Martin and Radak, Zsolt and Chamberlain, Jeffrey S. and Bakovic, Marica and Banka, Siddharth and Penninger, Josef M.}, issn = {2522-5812}, journal = {Nature Metabolism}, keywords = {Cell Biology, Physiology (medical), Endocrinology, Diabetes and Metabolism, Internal Medicine}, pages = {495--515}, publisher = {Springer Nature}, title = {{PCYT2-regulated lipid biosynthesis is critical to muscle health and ageing}}, doi = {10.1038/s42255-023-00766-2}, volume = {5}, year = {2023}, } @article{12756, abstract = {ESCRT-III family proteins form composite polymers that deform and cut membrane tubes in the context of a wide range of cell biological processes across the tree of life. In reconstituted systems, sequential changes in the composition of ESCRT-III polymers induced by the AAA–adenosine triphosphatase Vps4 have been shown to remodel membranes. However, it is not known how composite ESCRT-III polymers are organized and remodeled in space and time in a cellular context. Taking advantage of the relative simplicity of the ESCRT-III–dependent division system in Sulfolobus acidocaldarius, one of the closest experimentally tractable prokaryotic relatives of eukaryotes, we use super-resolution microscopy, electron microscopy, and computational modeling to show how CdvB/CdvB1/CdvB2 proteins form a precisely patterned composite ESCRT-III division ring, which undergoes stepwise Vps4-dependent disassembly and contracts to cut cells into two. These observations lead us to suggest sequential changes in a patterned composite polymer as a general mechanism of ESCRT-III–dependent membrane remodeling.}, author = {Hurtig, Fredrik and Burgers, Thomas C.Q. and Cezanne, Alice and Jiang, Xiuyun and Mol, Frank N. and Traparić, Jovan and Pulschen, Andre Arashiro and Nierhaus, Tim and Tarrason-Risa, Gabriel and Harker-Kirschneck, Lena and Löwe, Jan and Šarić, Anđela and Vlijm, Rifka and Baum, Buzz}, issn = {2375-2548}, journal = {Science Advances}, number = {11}, publisher = {American Association for the Advancement of Science}, title = {{The patterned assembly and stepwise Vps4-mediated disassembly of composite ESCRT-III polymers drives archaeal cell division}}, doi = {10.1126/sciadv.ade5224}, volume = {9}, year = {2023}, } @article{12757, abstract = {My group and myself have studied respiratory complex I for almost 30 years, starting in 1994 when it was known as a L-shaped giant ‘black box' of bioenergetics. First breakthrough was the X-ray structure of the peripheral arm, followed by structures of the membrane arm and finally the entire complex from Thermus thermophilus. The developments in cryo-EM technology allowed us to solve the first complete structure of the twice larger, ∼1 MDa mammalian enzyme in 2016. However, the mechanism coupling, over large distances, the transfer of two electrons to pumping of four protons across the membrane remained an enigma. Recently we have solved high-resolution structures of mammalian and bacterial complex I under a range of redox conditions, including catalytic turnover. This allowed us to propose a robust and universal mechanism for complex I and related protein families. Redox reactions initially drive conformational changes around the quinone cavity and a long-distance transfer of substrate protons. These set up a stage for a series of electrostatically driven proton transfers along the membrane arm (‘domino effect'), eventually resulting in proton expulsion from the distal antiporter-like subunit. The mechanism radically differs from previous suggestions, however, it naturally explains all the unusual structural features of complex I. In this review I discuss the state of knowledge on complex I, including the current most controversial issues.}, author = {Sazanov, Leonid A}, issn = {1470-8728}, journal = {The Biochemical Journal}, number = {5}, pages = {319--333}, publisher = {Portland Press}, title = {{From the 'black box' to 'domino effect' mechanism: What have we learned from the structures of respiratory complex I}}, doi = {10.1042/BCJ20210285}, volume = {480}, year = {2023}, } @article{12758, abstract = {AlphaFold changed the field of structural biology by achieving three-dimensional (3D) structure prediction from protein sequence at experimental quality. The astounding success even led to claims that the protein folding problem is “solved”. However, protein folding problem is more than just structure prediction from sequence. Presently, it is unknown if the AlphaFold-triggered revolution could help to solve other problems related to protein folding. Here we assay the ability of AlphaFold to predict the impact of single mutations on protein stability (ΔΔG) and function. To study the question we extracted the pLDDT and metrics from AlphaFold predictions before and after single mutation in a protein and correlated the predicted change with the experimentally known ΔΔG values. Additionally, we correlated the same AlphaFold pLDDT metrics with the impact of a single mutation on structure using a large scale dataset of single mutations in GFP with the experimentally assayed levels of fluorescence. We found a very weak or no correlation between AlphaFold output metrics and change of protein stability or fluorescence. Our results imply that AlphaFold may not be immediately applied to other problems or applications in protein folding.}, author = {Pak, Marina A. and Markhieva, Karina A. and Novikova, Mariia S. and Petrov, Dmitry S. and Vorobyev, Ilya S. and Maksimova, Ekaterina and Kondrashov, Fyodor and Ivankov, Dmitry N.}, issn = {1932-6203}, journal = {PLoS ONE}, number = {3}, publisher = {Public Library of Science}, title = {{Using AlphaFold to predict the impact of single mutations on protein stability and function}}, doi = {10.1371/journal.pone.0282689}, volume = {18}, year = {2023}, } @article{12759, abstract = {Stereological methods for estimating the 3D particle size and density from 2D projections are essential to many research fields. These methods are, however, prone to errors arising from undetected particle profiles due to sectioning and limited resolution, known as ‘lost caps’. A potential solution developed by Keiding, Jensen, and Ranek in 1972, which we refer to as the Keiding model, accounts for lost caps by quantifying the smallest detectable profile in terms of its limiting ‘cap angle’ (ϕ), a size-independent measure of a particle’s distance from the section surface. However, this simple solution has not been widely adopted nor tested. Rather, model-independent design-based stereological methods, which do not explicitly account for lost caps, have come to the fore. Here, we provide the first experimental validation of the Keiding model by comparing the size and density of particles estimated from 2D projections with direct measurement from 3D EM reconstructions of the same tissue. We applied the Keiding model to estimate the size and density of somata, nuclei and vesicles in the cerebellum of mice and rats, where high packing density can be problematic for design-based methods. Our analysis reveals a Gaussian distribution for ϕ rather than a single value. Nevertheless, curve fits of the Keiding model to the 2D diameter distribution accurately estimate the mean ϕ and 3D diameter distribution. While systematic testing using simulations revealed an upper limit to determining ϕ, our analysis shows that estimated ϕ can be used to determine the 3D particle density from the 2D density under a wide range of conditions, and this method is potentially more accurate than minimum-size-based lost-cap corrections and disector methods. Our results show the Keiding model provides an efficient means of accurately estimating the size and density of particles from 2D projections even under conditions of a high density.}, author = {Rothman, Jason Seth and Borges Merjane, Carolina and Holderith, Noemi and Jonas, Peter M and Angus Silver, R.}, issn = {1932-6203}, journal = {PLoS ONE}, number = {3 March}, publisher = {Public Library of Science}, title = {{Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy}}, doi = {10.1371/journal.pone.0277148}, volume = {18}, year = {2023}, } @inproceedings{12760, abstract = {Dynamic programming (DP) is one of the fundamental paradigms in algorithm design. However, many DP algorithms have to fill in large DP tables, represented by two-dimensional arrays, which causes at least quadratic running times and space usages. This has led to the development of improved algorithms for special cases when the DPs satisfy additional properties like, e.g., the Monge property or total monotonicity. In this paper, we consider a new condition which assumes (among some other technical assumptions) that the rows of the DP table are monotone. Under this assumption, we introduce a novel data structure for computing (1 + ϵ)-approximate DP solutions in near-linear time and space in the static setting, and with polylogarithmic update times when the DP entries change dynamically. To the best of our knowledge, our new condition is incomparable to previous conditions and is the first which allows to derive dynamic algorithms based on existing DPs. Instead of using two-dimensional arrays to store the DP tables, we store the rows of the DP tables using monotone piecewise constant functions. This allows us to store length-n DP table rows with entries in [0, W] using only polylog(n, W) bits, and to perform operations, such as (min, +)-convolution or rounding, on these functions in polylogarithmic time. We further present several applications of our data structure. For bicriteria versions of k-balanced graph partitioning and simultaneous source location, we obtain the first dynamic algorithms with subpolynomial update times, as well as the first static algorithms using only near-linear time and space. Additionally, we obtain the currently fastest algorithm for fully dynamic knapsack.}, author = {Henzinger, Monika H and Neumann, Stefan and Räcke, Harald and Schmid, Stefan}, booktitle = {40th International Symposium on Theoretical Aspects of Computer Science}, isbn = {9783959772662}, issn = {1868-8969}, location = {Hamburg, Germany}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Dynamic maintenance of monotone dynamic programs and applications}}, doi = {10.4230/LIPIcs.STACS.2023.36}, volume = {254}, year = {2023}, } @article{12761, abstract = {We consider the fluctuations of regular functions f of a Wigner matrix W viewed as an entire matrix f (W). Going beyond the well-studied tracial mode, Trf (W), which is equivalent to the customary linear statistics of eigenvalues, we show that Trf (W)A is asymptotically normal for any nontrivial bounded deterministic matrix A. We identify three different and asymptotically independent modes of this fluctuation, corresponding to the tracial part, the traceless diagonal part and the off-diagonal part of f (W) in the entire mesoscopic regime, where we find that the off-diagonal modes fluctuate on a much smaller scale than the tracial mode. As a main motivation to study CLT in such generality on small mesoscopic scales, we determine the fluctuations in the eigenstate thermalization hypothesis (Phys. Rev. A 43 (1991) 2046–2049), that is, prove that the eigenfunction overlaps with any deterministic matrix are asymptotically Gaussian after a small spectral averaging. Finally, in the macroscopic regime our result also generalizes (Zh. Mat. Fiz. Anal. Geom. 9 (2013) 536–581, 611, 615) to complex W and to all crossover ensembles in between. The main technical inputs are the recent multiresolvent local laws with traceless deterministic matrices from the companion paper (Comm. Math. Phys. 388 (2021) 1005–1048).}, author = {Cipolloni, Giorgio and Erdös, László and Schröder, Dominik J}, issn = {1050-5164}, journal = {Annals of Applied Probability}, number = {1}, pages = {447--489}, publisher = {Institute of Mathematical Statistics}, title = {{Functional central limit theorems for Wigner matrices}}, doi = {10.1214/22-AAP1820}, volume = {33}, year = {2023}, } @article{12762, abstract = {Neurons in the brain are wired into adaptive networks that exhibit collective dynamics as diverse as scale-specific oscillations and scale-free neuronal avalanches. Although existing models account for oscillations and avalanches separately, they typically do not explain both phenomena, are too complex to analyze analytically or intractable to infer from data rigorously. Here we propose a feedback-driven Ising-like class of neural networks that captures avalanches and oscillations simultaneously and quantitatively. In the simplest yet fully microscopic model version, we can analytically compute the phase diagram and make direct contact with human brain resting-state activity recordings via tractable inference of the model’s two essential parameters. The inferred model quantitatively captures the dynamics over a broad range of scales, from single sensor oscillations to collective behaviors of extreme events and neuronal avalanches. Importantly, the inferred parameters indicate that the co-existence of scale-specific (oscillations) and scale-free (avalanches) dynamics occurs close to a non-equilibrium critical point at the onset of self-sustained oscillations.}, author = {Lombardi, Fabrizio and Pepic, Selver and Shriki, Oren and Tkačik, Gašper and De Martino, Daniele}, issn = {2662-8457}, journal = {Nature Computational Science}, pages = {254--263}, publisher = {Springer Nature}, title = {{Statistical modeling of adaptive neural networks explains co-existence of avalanches and oscillations in resting human brain}}, doi = {10.1038/s43588-023-00410-9}, volume = {3}, year = {2023}, } @article{12763, abstract = {Kleinjohann (Archiv der Mathematik 35(1):574–582, 1980; Mathematische Zeitschrift 176(3), 327–344, 1981) and Bangert (Archiv der Mathematik 38(1):54–57, 1982) extended the reach rch(S) from subsets S of Euclidean space to the reach rchM(S) of subsets S of Riemannian manifolds M, where M is smooth (we’ll assume at least C3). Bangert showed that sets of positive reach in Euclidean space and Riemannian manifolds are very similar. In this paper we introduce a slight variant of Kleinjohann’s and Bangert’s extension and quantify the similarity between sets of positive reach in Euclidean space and Riemannian manifolds in a new way: Given p∈M and q∈S, we bound the local feature size (a local version of the reach) of its lifting to the tangent space via the inverse exponential map (exp−1p(S)) at q, assuming that rchM(S) and the geodesic distance dM(p,q) are bounded. These bounds are motivated by the importance of the reach and local feature size to manifold learning, topological inference, and triangulating manifolds and the fact that intrinsic approaches circumvent the curse of dimensionality.}, author = {Boissonnat, Jean Daniel and Wintraecken, Mathijs}, issn = {2367-1734}, journal = {Journal of Applied and Computational Topology}, pages = {619--641}, publisher = {Springer Nature}, title = {{The reach of subsets of manifolds}}, doi = {10.1007/s41468-023-00116-x}, volume = {7}, year = {2023}, }